Project Summary Currently, serum prostate specific antigen screening has demonstrated its importance in detecting early-stage prostate cancer (PCa). Unfortunately, at present, clinically known measures are often insufficient to differentiate aggressive from indolent PCa, predict overall disease status and, more critically, predict outcomes for patients of these early-stage diseases. Thus, the challenge seen in PCa clinic urges development of novel methods to identify patients whose tumor aggressive potential warrants decisive action, while preventing overtreatment of the majority indolent population. In this project, collectively considering PCa characteristics reported in literature, the availability of new technologies, and our significant recent observations, we propose to investigate the feasibility of developing a hyperpolarized (HP) carbon-13 (13C) magnetic resonance spectroscopy imaging (MRSI) paradigm to measure the dynamics of polyamine ornithine initiated synthetic pathways in prostate that have been reported to reflect PCa enzymatic bioactivities associated with disease aggressiveness. The project will explore and test aspects included in the following two specific aims: 1) Physiological and pathological feasibility studies of enzymatic polyamine synthetic rates and polyamine biodistributions in the prostate and other critical organs for healthy and PCa rat models with ex vivo tissue measurements, and comparing them with those of pyruvate that have been extensively reported, and 2) Technical feasibility studies for developing in vivo HP sequential [1-13C]Ornithine and [1-13C]Pyruvate protocols with healthy rat models and for testing in vitro mechanisms to increase [1,2-13C]Orn T1 lifetime in order to prolong the measurable 13C polyamine transitions. The success of this exploratory project will lead us to the design of polyamine and pyruvate co-agent HP 13C MRSI clinical trials to imaging benign and PCa tissues simultaneously, and respectively, and test the efficacy of utilizing enzymatic activities of polyamine pathways in characterization of human PCa status.